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Status |
Public on Mar 01, 2020 |
Title |
Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection [II] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
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Overall design |
QHR-4C profiles of P0 wild type (WT) and CBS-deletion mouse cortex were generated by deep sequencing using Illumina HiSeq X-ten
CBS deletion mouse lines used in this study (UCSC mouse July 2007(mm9) referance genome): CBSa del chr18:38,001,106-chr18:38,001,113 CBSbcd del chr18:38,011,224-chr18:38,037,839 CBSbc del chr18:38,011,224-chr18:38,013,147 CBSde del chr18:38,036,567-chr18:38,040,872 CBSd del chr18:38,036,568-chr18:38,037,818 CBSb-e del chr18:38011471-chr18:38040871 CBSe del chr18:38,039,423-chr18:38,040,879
Please note that the GSM4046041-GSM4046056 sample records have been moved to GSE211024 on Aug 11, 2022 as per submitter's request.
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Contributor(s) |
Jia Z, Ge X, Wu Y, Wu Q |
Citation(s) |
32293525 |
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Submission date |
Aug 26, 2019 |
Last update date |
Aug 13, 2022 |
Contact name |
Xiao Ge |
Organization name |
Shanghai JiaoTong University
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Street address |
No. 800 Dongchuan Road
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City |
Shanghai |
ZIP/Postal code |
200240 |
Country |
China |
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Platforms (1) |
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Samples (44)
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This SubSeries is part of SuperSeries: |
GSE138646 |
Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection |
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Relations |
BioProject |
PRJNA562270 |
SRA |
SRP219361 |
Supplementary file |
Size |
Download |
File type/resource |
GSE136328_RAW.tar |
118.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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